Factors are sought which contribute to insulin antagonism in clinical states of obesity, maturity-onset diabetes, hyperparathyroidism, pregnancy and following sex steroid and prolactin administration. Correlations with plasma alpha cell glucagon disturbances are made. In addition, the female rat animal model is employed to examine: a) bihormonal insulin-glucagon secretion in the perifused islet system under conditions that simulate the clinical states and b) the perfused skeletal muscle sytem to assess the effects of these states on insulin sensitivity as measured by glucose uptake and amino acid release. To further our knowledge regarding events that control pancreatic islet hormonal secretion, single cells from perifused pancreatic islets that are stimulated with various secretagogues are examined at sequential time intervals by energy dispersive X-ray analysis for trace element content. This provides a means for relating changes in trace elements to augmentation or suppression of beta cell insulin or alpha cell glucagon release.